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Information on EC 5.6.1.6 - channel-conductance-controlling ATPase and Organism(s) Homo sapiens and UniProt Accession P13569

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IUBMB Comments
ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. The enzyme is found in animals, and in humans its absence brings about cystic fibrosis. Unlike most of the ABC transporters, chloride pumping is not directly coupled to ATP hydrolysis. Instead, the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The enzyme is also involved in the functioning of other transmembrane channels.
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Homo sapiens
UNIPROT: P13569
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
+
closed Cl- channel
=
+
+
open Cl- channel
Synonyms
cystic fibrosis transmembrane conductance regulator, cystic fibrosis transmembrane regulator, cftr channel, cftr cl- channel, cystic fibrosis conductance regulator, abcc7, epithelial basolateral chloride conductance regulator, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CFTR channel
-
cystic fibrosis transmembrane conductance regulator
-
transmembrane domains of cystic fibrosis transmembrane conductance regulator
-
transmembrane domains of cystic fibrosis transmembrane conductance regulator channel
-
CFTR Cl- channel
-
-
cystic fibrosis conductance regulator
-
-
cystic fibrosis transmembrane conductance regulator
cystic-fibrosis membrane-conductance protein
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + closed Cl- channel = ADP + phosphate + open Cl- channel
show the reaction diagram
ATP + H2O + closed Cl- channel = ADP + phosphate + open Cl- channel
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
transmembrane transport
-
-
-
-
hydrolysis of phosphate bond
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (channel-conductance-controlling)
ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. The enzyme is found in animals, and in humans its absence brings about cystic fibrosis. Unlike most of the ABC transporters, chloride pumping is not directly coupled to ATP hydrolysis. Instead, the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The enzyme is also involved in the functioning of other transmembrane channels.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-methyl-dCTP + H2O + closed Cl- channel
5-methyl-dCDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
7-methyl-GTP + H2O + closed Cl- channel
7-methyl-GDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
show the reaction diagram
CTP + H2O + closed Cl- channel
CDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
dATP + H2O + closed Cl- channel
dADP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
dCTP + H2O + closed Cl- channel
dCDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
dGTP + H2O + closed Cl- channel
dGDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
dTTP + H2O + closed Cl- channel
dTDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
dUTP + H2O + closed Cl- channel
dUDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
GTP + H2O + closed Cl- channel
GDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
TTP + H2O + closed Cl- channel
TDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
UTP + H2O + closed Cl- channel
UDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
?
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
show the reaction diagram
ATP + H2O + closed I- channel
ADP + phosphate + open I- channel
show the reaction diagram
-
-
-
-
?
GTP + H2O + closed Cl- channel
GDP + phosphate + open Cl- channel
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
show the reaction diagram
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
show the reaction diagram
ATP + H2O + closed I- channel
ADP + phosphate + open I- channel
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
-
coordinated by residues G551, S549, and L548. Highly activating the chloride channel activity of CFTR mutant G551D in absence of ATP, but not of wild-type CFTR or mutant G551A
Co2+
-
best divalent metal activator
Mn2+
-
activates
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-sulfonatoethyl methanethiosulfonate
enzyme residues A299, R303, N306, S307, F310, and F311 are accessible to intracellular 2-sulfonatoethyl methanethiosulfonate in both the open and closed states
Fe3+
binds at the interface of the regulatory (R) domain and intracellular loop (ICL) 3
forskolin
abolishes the enzyme activity, which is reversible by DTT
genistein
bindings of genistein and ATP are competitive
glibencalmide
an open-channel blocker
N6-(2-phenylethyl)-ATP
competitive with ATP, binds to ATP-binding pocket 1
P1,P5-di(adenosine-5') pentaphosphate
Ap5A, an adenylate kinase inhibitor that partially inhibits wild-type CFTR, and inhibition can be attenuated by high ATP concentrations
[Au(CN)2]-
2-(pyridin-4-yl)-4H-benzo[h]chromen-4-one
-
i.e. UCCF-029. Concentrations below 50 nM increase the open probability of the channel, favouring the channel transition to the an activated state. Levels above 50 nM determine inhibition of the channel by a reduction of the open time. UCCF-029 does not interfere with binding of ATP
3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone
-
CFTR(inh)-172, potent CFTR inhibitor, exerts nonspecific effects regarding reactive oxygen species production, mitochondrial failure, and activation of the NF-kappa B signaling pathway, independently of CFTR inhibition
5-nitro-2(3-phenylpropylamino)benzoate
-
-
5-[(4-carboxyphenyl)methylene]-2-thioxo-3-[(3-trifluoromethyl)phenyl]4-thiazolidinone
-
-
8-(4-chlorophenylthio)-AMP
-
the ATPase activity of the enzyme is reduced in the presence of higher concentrations of 8-(4-chlorophenylthio)-AMP
8-azido-ATP
-
is retained at nucleotide-binding domain 1, NBD1 at low temperature even in the absence of bivalent cations
adenylyl-imidodiphosphate
-
modulation of the on-rate of venom binding for intraburst block
adenylyliminodiphosphate
-
-
ATP-P3-[1-(2-nitrophenyl)ethyl]ester
-
-
Au(CN)2-
-
inhibits the ion channel function
bumetanide
-
blocks CFTR
Cd2+
-
-
CFTRinh-172
CFTRinh172
-
blocks CFTR
CL1 peptide
-
both intrinsic ATPase activity and channel gating are inhibited severely by CL1 peptide
-
detergent SB-300
-
blocks forskolin-stimulated CFTR Cl- secretion by 92.2%
-
detergent SB-303
-
decreases stimulated CFTR Cl- currents by 98%
-
diphenylamine-2-carboxylate
-
-
glibenclamide
-
-
glipizide
-
-
glybenclamide
-
-
GlyH-101
-
specific inhibitor
N-(2-naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide
-
GlyH-101, potent CFTR inhibitor, exerts nonspecific effects regarding reactive oxygen species production, mitochondrial failure, and activation of the NF-kappa B signaling pathway, independently of CFTR inhibition
phosphatidylinositol 4,5-bisphosphate
-
applied to phosphorylated CTFR may inhibit the CTFR chloride current
Tolbutamide
-
-
vanadate
venom
-
from Leirus quinquestriatus hebraeus, reversly inhibits CFTR, when applied to its cytoplasmic surface, preferentially binds to closed CFTR channels, effectiveness of macroscopic inhibition depends on the level of CFTR channel activity, the venom also binds to CFTR during intraburst closings, efficacy of intraburst inhibition at the single-channel level depends on open probability
-
VRT-532
-
i.e. 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol, the ATPase activity of the purified and reconstituted mutant DELTAPhe508-CFTR is directly modulated and ATP turnover is decreased by binding of VRT-532, but VRT-532 stimulates channel function of DELTAPhe508-CFTR in cells. VRT-532 binding induces a change in conformational stability of the C-terminal half of DELATPhe508-CFTR
Zn2+
-
Zn2+ inhibits channel activity in a dose- and Cl--dependent manner. Cl--dependent Zn2+ inhibition is weakened at higher Zn2+ concentrations, Zn2+ affinity is stronger in the resting state than in the activated state, and activation current noises are decreased by external Zn2+ binding
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
half-maximal activation by 0.05 mM
curcumin
molecular basis for Fe(III)-independent curcumin potentiation of cystic fibrosis transmembrane conductance regulator activity, overview. Highly conserved aromatic and positively charged residues at the ICL1/ICL4 interface and phosphorylation site S813 are sensitive to curcumin regardless of whether Fe3+ and nucleotide-binding domain 2 are removed. Spontaneous disulfide cross-linking between curcumin-sensitive ICL1 and S795 is observed to be enough to promote channel opening as curcumin does. Curcumin may potentiate CFTR activity not only by removing inhibitory Fe3+ to release the R domain from ICL3 but also by stabilizing the stimulatory R-ICL1/ICL4 interactions
1,10-phenanthroline
-
-
1,3-diallyl-8-cyclohexylxanthine
-
-
2-(pyridin-4-yl)-4H-benzo[h]chromen-4-one
-
i.e. UCCF-029. Concentrations below 50 nM increase the open probability of the channel, favouring the channel transition to the an activated state. Levels above 50 nM determine inhibition of the channel by a reduction of the open time. UCCF-029 does not interfere with binding of ATP
2-pyrimidin-7,8-benzoflavone
-
induces significant conformational changes of the isolated NBD1/NBD2 dimer in solution. 2-pyrimidin-7,8-benzoflavone does not modify the ATP binding constant, but reduces the ATP hydrolysis activity of the NBD1/NBD2 mixture. In absence of ATP, the NBD1/NBD2 dimer is disrupted by the compound, but in the presence of 2 mM ATP, the two NBDs keep dimerised, and a major change in the size and the shape of the structure is observed
3-isobutyl-1-methylxanthine
3-isobutyl-methylxanthine
-
-
8-(4-chlorophenylthio)-AMP
-
the ATPase activity of the enzyme is enhanced in the presence of very low concentrations of 8-(4-chlorophenylthio)-AMP
8-cyclopentyl-1,3-dipropylxanthine
-
activates prephosphorylated CFTR by binding directly to CFTR
BeF3
-
amount of Cl- currents is less than 30% that of the wild-type CFTR
benzimidazolone compounds
-
-
-
benzoquinolizinium compounds
-
-
-
calnexin
-
Dependence on calnexin for proper assembly of CFTR’s membrane spanning domains exists, also efficient folding of NBD2 is dependent upon calnexin binding to CFTR, but calnexin is not essential for wild-type CFTR or mutant CFTR DELTAF508 degradation
-
DiBu-cAMP
-
-
diphosphate
flavonoid
-
-
fluorescein derivative
-
-
-
forskolin
genistein
-
activates prephosphorylated CFTR by binding directly to CFTR, higher concentrations inhibit
isoproterenol
-
-
KCN
-
without cAMP stimulation, KCN treatment increases CFTR Cl- conductance by 1.95fold, whereas after cAMP stimulation KCN treatment increases conductance by 13.7fold
lubiprostone
-
lubiprostone and forskolin activate the same pool of apical Cl- channels, lubiprostone induces the secretory response in intestinal epithelium involving the enzyme. Lubiprostone enhances intestinal Cl- and fluid secretion via prostanoid receptor signaling, triggering activation of CFTR. The EP4-type prostanoid receptor antagonist L-161982 blocks the lubiprostone response. Lubiprostone enhances Cl- secretion across human large and mall intestinal epithelium through a CFTR-dependent pathway
NS-004
-
activates prephosphorylated CFTR by binding directly to CFTR
phosphatidylinositol 4,5-bisphosphate
-
activation of CTFR, which results in ATP responsiveness, AtP opens nonphosphorylated CTFR after application of phosphatidylinositol 4,5-bisphosphate
phosphatidylserine
-
the enzyme requires phosphatidylserine for maximum ATPase activity
VO43-
-
prolongs the duration of the burst of channel activity
VRT-532
-
i.e. 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol, the ATPase activity of the purified and reconstituted mutant DELTAPhe508-CFTR is directly modulated and ATP turnover is decreased by binding of VRT-532, but VRT-532 stimulates channel function of DELTAPhe508-CFTR in cells. VRT-532 binding induces a change in conformational stability of the C-terminal half of DELATPhe508-CFTR
xanthine
-
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00331 - 2.2
ATP
0.15
MgATP2-
-
pH 7.5, 37°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22 - 14
ATP
additional information
additional information
-
60-120 gating events per min
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0026
CFTRinh-172
Homo sapiens
-
pH 7.5, 37°C, inhibition of ATPase activity of mutant DELTAPhe508-CFTR
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.06
-
with ATP as substrate
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
adenylate kinase assay at
7.2
-
single channel activity assay at
7.5
-
ATPase assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23 - 26
37
adenylate kinase assay at
22
-
ion channel activity assay at room temperature
27
-
ion channel assay at
30
-
single channel activity assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
26 - 37
-
at 26°C dramatic increase in CFTR protein levels as compared to the protein isolated from the tissue incubated at 37°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
expression comparable to the expression in alveolar epithelial type II cell
Manually annotated by BRENDA team
-
freshly excised rectal biopsies
Manually annotated by BRENDA team
-
area over the scapula, primary cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
F508del CFTR in BHK cells
Manually annotated by BRENDA team
-
recycling
Manually annotated by BRENDA team
-
immature
-
Manually annotated by BRENDA team
additional information
-
the wild-type and G551D CFTR have overlapping postendocytic membrane trafficking. G551D like its wild-type counterpart recycles back to the cell surface and largely avoids lysosomal delivery
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
malfunction
metabolism
-
Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. The small molecule apoptozole has high cellular potency to promote membrane trafficking of mutant DeltaF508 and its chloride channel activity in cystic fibrosis cells. Apoptozole inhibits the ATPase activity of Hsc70 by binding to its ATPase domain and apoptozole suppresses ubiquitination of DeltaF508 maybe by blocking interaction of the mutant with Hsc70 and E3 ubiquitin ligase CHIP, and, as a consequence, it enhances membrane trafficking of the mutant
physiological function
-
the channel activity of the enzyme is required for epithelial regulatory volume decrease
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CFTR_HUMAN
1480
11
168142
Swiss-Prot
Mitochondrion (Reliability: 5), Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
165000
-
SDS-PAGE, mannose rich isoform of CFTR
170000
-
1 * 170000, CFTR exitsts as monomers and multimers, the monomer is the minimum functional unit required for channel and ATPase activity, SDS-PAGE
180000
-
x * 180000, untagged CFTR, SDS-PAGE, x * 210000, GFP-tagged CFTR, SDS-PAGE
195000
-
SDS-PAGE or immunoprecipitation, complex-glycosylated isoform of CFTR
210000
-
x * 180000, untagged CFTR, SDS-PAGE, x * 210000, GFP-tagged CFTR, SDS-PAGE
212000
-
gel filtration
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 170000, CFTR exitsts as monomers and multimers, the monomer is the minimum functional unit required for channel and ATPase activity, SDS-PAGE
multimer
-
CFTR exitsts as monomers and multimers
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
enzyme CFTR core glycosylation occurs in the endoplasmic reticulum
phosphoprotein
glycoprotein
phosphoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant enzyme F508del, microbatch method, using 40% (w/v) PEG 400, 100 mM NH4Cl, and 100 mM MES, pH 6.0
3D structure constructed by molecular modeling. Residue F508 mediates a tertiary interaction between the surface of nucleotide-binding domain 1 and a cytoplasmic loop in the C-terminal membrane-spanning domain
-
by hanging drop method, at 20 A resolution in the xy plane, at 30 A resolution along z plane, two crystal forms, one with a roughly hexagonal profile, the other with an opened-out triangular profile, the two conformations are in presence of a nucleotide, which may be related to the role of CFTR as an ion channel rather than a transporter, and may represent the open and closed states of the channel
-
cryo-electron microscopy
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A299C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
A326C
site-directed mutagenesis, the substituted cysteine does not respond to neither internal nor external 2-sulfonatoethyl methanethiosulfonate and is inaccessible to channel-permeant thiol-specific reagent [Au(CN)2]-
A462F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 1, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The A462F mutation interfers with processing and trafficking to the cell membrane
D1370N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
D572N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
D924R
site-directed mutagenesis, the mutant shows brief transitions to all conductance levels, it can reach the open state but not stably
D993R
site-directed mutagenesis, the mutant opens to all 3 levels, but none are stable. The mutant can reach the open state but not stably
DELTAF508
in-frame deletion without a phenylalanine residue at position 508 within nucleotide –binding domain 1: mass spectral measurements of backbone amide 1H/2H exchange rates in reveal that mutant DELTAF508 increases backbone dynamics at residues 509-511 and the adjacent protein segments but not elsewhere in NBD1. These measurements also confirm a high level of flexibility in the protein segments exhibiting variable conformations in the crystal structures
DELTAF508/F409L/F4929S/F433L/G550E/R553Q/R555K/H667R
mutant bearing an in-frame deletion without a phenylalanine residue at position 508 within nucleotide-binding domain 1 as well as several solubilizing mutations: Crystal structure refined at 2.55 A: The side chain of residue V510 in this loop is completely solvent exposed
DELTAF508/F429S/F494N/Q637R
mutant bearing an in-frame deletion without a phenylalanine residue at position 508 within nucleotide-binding domain 1 as well as several solubilizing mutations: Crystal structure refined at 2.3 A: The side chain of residue V510 in this loop is completely solvent exposed
DELTAF508/F494N/Q637R
mutant bearing an in-frame deletion without a phenylalanine residue at position 508 within nucleotide-binding domain 1 as well as several solubilizing mutations: Crystal structure refined at 2.05 A: The side chain of residue V510 in this loop is completely solvent exposed
F310C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
F311C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
F337C
site-directed mutagenesis
F409L/F4929S/F433L/G550E/R553Q/R555K/H667R
mutant bearing no in-frame deletion of a phenylalanine residue at position 508 but with several solubilizing mutations: Crystal structure refined at 2.55 A: The side chain of residue V510 in this loop is buried
F508del
the in-frame deletion causes cystic fibrosis
G1349D
site-directed mutagenesis, a mutation associated with the genetic disease cystic fibrosis
G134D/F337C
site-directed mutagenesis, increased accessibility of the side chain of 338C in the closed state compared to mutant F337C
G134D/T338C
site-directed mutagenesis, limited accessibility of the side chain of 338C in the closed state compared to mutant T338C
G551D
G551D/Y1219F
increased ATP washout compared to mutant G551D
G551D/Y1219G
G551D/Y1219I
increased ATP washout compared to mutant G551D
G551E
site-directed mutagenesis, the mutant exhibits a similar phenotype like mutant G551D
G551K
site-directed mutagenesis, the mutant does not exhibit a similar phenotype like mutant G551D
G551S
site-directed mutagenesis, the mutant does not exhibit a similar phenotype like mutant G551D
K1250A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
K464A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
L323C
site-directed mutagenesis, the substituted cysteine does not respond to neither internal nor external 2-sulfonatoethyl methanethiosulfonate and is inaccessible to channel-permeant thiol-specific reagent [Au(CN)2]-
N306C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
P355A
gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP)
P355F
gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP)
P355S
gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP)
Q1291A
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current
Q1291F
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current. The Q1291F mutation disrupts photolabeling of the AMP-binding site with 8-N3-AMP
Q1291G
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current
Q1291H
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current
Q1291W
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current
Q1291Y
mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current
R303C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
R334C
site-directed mutagenesis
R347A
site-directed mutagenesis, the mutant emphasizes s1 state, brief transitions to s2 state and the open state, it can reach the open state but not stably
R347A/R352A
site-directed mutagenesis, the mutant opens to all 3 levels, s1 state is much more stable than in the wild-type, s2 state is unstable, the open state is unstable. The mutant can reach the open state but not stably
R347D
site-directed mutagenesis, the mutant emphasizes s1 state, no transitions to s2 state and the open state, the mutant cannot reach the open state
R347D/D924R
site-directed mutagenesis, the mutant emphasizes s2 state, rare and brief transitions to the open state, it can reach the open state but not stably
R347D/D924R/D993R
site-directed mutagenesis, the mutant opens to all 3 levels, s1 state is much more stable than in the wild-type, s2 state is relatively stabilized, the open state is unstable. The mutant can reach the open state but not stably
R347D/D924R/R352E/D993R
site-directed mutagenesis, the mutant primarily flickers between s2 state and the open state, s1 state is much more stable than in the wild-type, the mutant shows slightly reduced single channel conductance, it can reach the open state but not stably
R347D/D993R
site-directed mutagenesis, the mutant shows very stable s2 state, but rare and brief transitions to both s1 state and the open state. It can reach the open state but not stably
R347K
site-directed mutagenesis, the mutant is wild-type-like
R352E
site-directed mutagenesis, the mutant opens to all 3 levels, s1 state is much more stable than in wild-type, s2 state is unstable, the open state is unstable. The mutant can reach the open state but not stably
R352E/D924R
site-directed mutagenesis, the mutant opens to all 3 levels, but none are stable. The mutant can reach the open state but not stably
R352E/D993R
site-directed mutagenesis, the mutant is wild type-like, with increased transitions to s1 and s2 states, it shows slightly reduced single-channel conductance, the impact on the open state is wild type-like
S1248F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 2, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The S1248F mutation does not interfere with processing and trafficking to the cell membrane
S307C
site-directed mutagenesis, the engineered cysteine reacts with intracellular 2-sulfonatoethyl methanethiosulfonate
T338C
site-directed mutagenesis
W401G
little effect on the sensitivity of the channel opening rate to the concentration of ATP, but shortens the open time constant
W401G/G551D
Y1219G
A196C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
A252C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
A367C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
D1152H
-
mutation in the CFTR gene causing cystic fibrosis
D572N
-
the mutation disrupts the interaction of ATP with ATP-binding site 1
DELTAF508
-
the deletion mutation is associated with cystic fibrosis
E1371Q
E1371S
E543C/T996C
-
cross-linking between residues T996C and E543C at the CL3/NBD1 interface rapidly and reversibly arrests channel gating
F337A
-
the mutation exhibits strong gain of function effects
F337C
F337L
-
the mutation exhibits strong gain of function effects
F337S
-
the mutation exhibits strong gain of function effects and markedly increases the activities of enzyme constructs that cannot be activated by ATP
F508C/E1371S
-
mutation in CFTR mutant lacking all cysteine residues due to replacement by alanine, except Cys590 and Cys592, which are replaced by leucine. Mutation F508C prevents the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Specifically, benzyl-methanethiosulphonate modification restores the gating behaviour to that of cysless E1371S
F508del
-
the mutation is associated with cystic fibrosis
G1349D
-
the mutation is associated with cystic fibrosis and greatly disturbs enzyme intraburst gating
G194C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
G241C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
G551A
-
the signature sequence mutant does not show activation of the the CFTR chloride channel activity by Cd2+ in contrast to mutant G551D
G551C
-
the signature sequence mutant shows activation of the the CFTR chloride channel activity by Cd2+ in contrast to the wild-type enzyme
G551D
G551D/W401F
-
mutation based on G551D in NBD1 signature motif, which completely abolishes ATP-induced openings of the channel. Additional mutation W401Y become ATP-responsive and are potentiated by N6-2-phenylethyl-ATP
G551D/W401Y
-
mutation based on G551D in NBD1 signature motif, which completely abolishes ATP-induced openings of the channel. Additional mutation W401Y become ATP-responsive and are potentiated by N6-2-phenylethyl-ATP
I331C
-
modification rate by methanethiosulfonate ethyl ammonium and (2-sulfonatoethyl) methanethiosulfonate is slower in the open state than in the closed state
K1250A
-
modulation of the on-rate of venom binding for intraburst block
K335C
K335E
-
conversion from a low I- permeability pore to a high I- permeability pore
K464A
K464H
-
mutant of the NBF1+R segment (nucleotide binding domain 1 and regulatory domain), Vmax is reduced about 50%
K95D
-
conversion from a low I- permeability pore to a high I- permeability pore
L172C/D1341C
-
the cross-linking between L172C of CL1 and D1341C of NBD2 rapidly and reversibly inhibited channel gating
L188C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
L197C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
L333C
-
modification rate by methanethiosulfonate ethyl ammonium and (2-sulfonatoethyl) methanethiosulfonate is slower in the open state than in the closed state
L548C
-
the signature sequence mutant shows activation of the the CFTR chloride channel activity by Cd2+ in contrast to the wild-type enzyme
M244C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
M245C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
N186C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
N189C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
N306C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
Q552C
-
the mutant does not show activation of the the CFTR chloride channel activity by Cd2+
R334C
R334C/E1126A
-
this double mutant is insensitive to 0.05 mM ZnCl2
R334W
-
amount of Cl- currents is less than 30% that of the wild-type CFTR
R347D
-
inhibition by 10 mM glutathione is higher than that of the wild-type enzyme. The Km-value for ATP in presence of protein kinase A is 3fold lower than that of the wild-type enzyme. The Km-value for ATP in absence of protein kinase A is 1.1fold higher than that of the wild-type enzyme
R347P
-
amount of Cl- currents is less than 30% that of the wild-type CFTR
R352E
-
channels bearing the R352E mutation exhibit frequent transitions to subconductance levels
R352E/D993R
-
channels bearing the revertant mutation R352E/D993R, primarily exhibit transitions to the full conductance level
R352E/E1104R
-
channels bearing the R352E mutation, or the double mutant R352E/E1104R, exhibit frequent transitions to subconductance levels
R352X
-
charge-destroying mutations at R352 alter CFTR single channel behavior
R553C
-
the mutant does not show activation of the the CFTR chloride channel activity by Cd2+
S307C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
S341C
-
the cysteine introduced at a position in the pore-lining TM6 region of CFTR is accessible to extracellular methanesulfonate reagents, charge-dependent changes in I-V shape in this mutant, indicating that deposition of charge at this position also alters anion movement in the pore
S549C
-
the signature sequence mutant shows activation of the the CFTR chloride channel activity by Cd2+ in contrast to the wild-type enzyme
S573E
-
mutation in nucleotide-binding domain 1, retains wild-type nucleotide binding affinity, does not confer additional ATPase activity to a heterodimer with nucleotide-binding domain 2 fragment mutant E1371Q
S768A
-
has higher activity than wild type channels, confirming the inhibitory influence of Ser 768
T1122C
-
0.05 mM ZnCl2 decreases the channel conductance of the mutant by about 55.2%. Internal curcumin reverses the Zn2+ inhibition
T122H
-
the mutant exhibits Cl--independent Zn2+ inhibition
T338C
T547C
-
the mutant does not show activation of the the CFTR chloride channel activity by Cd2+
V171C/L408C
-
the mutation has essentially no influence on gating
W1282X
-
mutation in the CFTR gene causing cystic fibrosis
W356C
-
[2-sulfonatoethyl] methanethiosulfonate-sensitive cysteine mutant
W401F
-
mutation W401Y facilitates channel closure from the lock-open state. W401F appears better than W401Y, which is in turn superior to tryptophan, in stabilizing the lock-open state
W401Y
-
mutation W401Y facilitates channel closure from the lock-open state. W401F appears better than W401Y, which is in turn superior to tryptophan, in stabilizing the lock-open state
Y1219F
-
mutation at NBD2, decreases ATP binding affinity and significantly increases the prevalence of the long-lasting opening events with a time constant of tens of seconds
Y1219G
-
mutation at NBD2, decreases ATP binding affinity and significantly increases the prevalence of the long-lasting opening events with a time constant of tens of seconds
Y1219I
-
mutation at NBD2, decreases ATP binding affinity and significantly increases the prevalence of the long-lasting opening events with a time constant of tens of seconds
Y1219W
-
mutation at NBD2, decreases ATP binding affinity and significantly increases the prevalence of the long-lasting opening events with a time constant of tens of seconds
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.8 - 8.8
-
when compared with the control (pH 7.3), acidifying pH to 6.3 or alkalinizing pH to 8.3 and 8.8 causes small reductions in the open-time constant of wild type enzyme. By contrast, the fast closed-time constant which describes the short-lived closures that interrupt open bursts, is greatly increased at pH 5.8 and 6.3
751395
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22 - 25
-
the enzyme, in the absence of lipid or nucleotide, is unstable at room temperature, losing approximately half its ATP hydrolysis activity over a 30 minute period. The melting temperature is 22.7°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in cycloheximide-treated clone C9 cells, the expressed GFP-CFTR exhibits a half-life of 48-72 h
-
in the absence of ATP, the Gd-HCl concentration to denature half of the proteins is about 2.2 M. A smaller Gd-HCl concentration,1.4 M, is needed to produce the same effect upon the application of 25 nM of 2-pyrimidin-7,8-benzoflavone
-
phosphatidylserine specifically stabilizes ATPase activity of the purified enzyme
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography and gel filtration
using Ni-NTA chromatography and gel filtration
by Ni-NTA resin
-
Ni-NTA matrix and subsequent WGA-agorse affinity step
-
of nucleotide binding domain 1 and nucleotide binding domain 2 from Sf9 cells
-
purification from Sf9 membranes
-
recombinant FLAG-tagged wild-type CFTR from HEK-293 cells by anti-FLAG and wheat germ agglutinin affinity chromatographies, and gel filtration
-
recombinant His-tagged mutant DELTAPhe508 from Sf9 cells by nickel affinity chromatography
-
the NBF1+R segment (nucleotide binding domain 1 and regulatory domain) and its mutant forms K464H and K464A
-
wild-type and mutant enzymes partially by subcellular fractionation
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli using as N-terminal His-tagged fusion protein
expression in CHO cell
expression in Xenopus laevis
recombinant expression of GFP-tagged wild-type and mutant enzymes in CHO cells
recombinant expression of wild-type and mutant enzymes in CHO cells
the CFTR gene is located on chromosome 7q31.31
transient expression of either wild-type or mutant enzymes in HeLa cell membranes using a vaccinia virus/T7 RNA polymerase expression system
transient expression of the enzyme in HEK-293T cells
transient expression of wild-type and mutant enzymes in HeLa cell membranes using a vaccinia virus/T7 RNA polymerase expression system, recombinant expression of wild-type and mutant enzymes in CHO cells and in HEK-293T cells, also using a vaccinia virus-T7 hybrid expression system for the latter cell type
transient recombinant expression of wild-type and mutant enzymes in HEK-293T cells
C terminally deca-histidine-tagged wild type human CFTR epxressed in baby hamster kidney-21 cells
-
CFTR genotyping in the Jewish and Arab population in Israel
-
coexpressed with murine or human epithelial Na+ channel in Xenopus laevis oocytes
-
coexpression of CFTR residues 1-414 with residues 433-1480, or residues 1-633 with 668-1480 in Xenopus laevis oocytes, to yield split CFTR channels, that lack most of the insertion or extension, respectively
-
expressed in Chinese hamster ovary and baby hamster kidney cells
-
expressed in D-727 cells
-
expressed in Escherichia coli in HEK-293T cells
-
expressed in Xenopus laevis oocytes
-
expression in BHK 21 cell
-
expression in BHK cell
-
expression in BHK cells
-
expression in CHO cell
-
expression in Escherichia coli
-
expression in Sf9 cells
-
expression in Xenopus laevis oocytes
-
expression in Xenopus oocytes
-
expression of a construct lacking Cys-residues, in CHO-cells
-
expression of a fusion protein of glutathione S-transferase and nucleotide binding domain 1
-
expression of a human CFTR variant in which all cysteines had been removed by mutagenesis, in baby hamster kidney cells
-
expression of FLAG-tagged wild-type CFTR in HEK-293 cells
-
expression of GFP-tagged CFTR in isogenic lung epithelial cell lines
-
expression of mutant DELTAPhe508 in BHK cells and as His-tagged protein in Spodoptera frugiperda Sf9 cells
-
expression of nucleotide binding domain 1 and nucleotide binding domain 2 separately and together in Sf9 cells
-
expression of recombinant NBD1, from residue 394 to residue 672, and NBD2, from residue 1191 to residue 1480, polypeptides in Escherichia coli
-
expression of the separate nucleotide-binding domains in Sf9 cell
-
expression of wild-type and mutant DELTAF508 in HEK-293 cells, and co-expression of CFTR halves
-
expression of wild-type and mutant enzymes in CHO cells
-
expression of wild-type and mutant enzymes in CHO cells and in HEK-293 cells
-
expression of wild-type and mutant enzymes in HEK-293 cells
-
full-length and truncated -fusion CFTR cDNAs are cloned into pGEM-4z vector and direct translation in a rabbit reticulocyte lysate system
-
mutant enzymes are expressed in HeLa cells
-
overexpression of the 3HA-tagged wild-type enzyme as well as of mutant G551D CFTR and mutant DELTAF508 CFTR in BHK, CFBE and HeLa cells
-
phylogenetic analysis and genotyping, expression of wild-type and mutant enzymes in Xenopus laevis oocytes
-
plasmid pQE60, encoding the CFTR amino acids 645-835 with COOH-terminal 6xHis tag, expressed in Escherichia coli, expression of Flag-wild type CFTR cRNA in Xenopus oocytes
-
stable expressed in CHO cells and transiently transfected in Sf9 cells
-
stable expression of wild-type and mutant DELTANBD2 CFTR in BHK-21 cell membranes
-
the four domains comprising CFTR are encoded by a single gene comprising an N-terminal TMD1 and NBD1 and a C-terminal TMD2 and NBD2
-
transfection of CHO cells
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
the guanidine hydrochloride-solubilized and denatured wild-type and mutant NBF1+R proteins can be renatured at 25°C upon rapid dilution with a buffered solution containing glycerol
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bradbury, N.A.
Intracellular CFTR localization and function
Physiol. Rev.
79
S175-191
1999
Homo sapiens
Manually annotated by BRENDA team
Sugita, M.; Yue, Y.; Foskett, J.K.
CFTR Cl- channel and CFTR-associated ATP channel: distinct pores regulated by common gates
EMBO J.
17
898-908
1998
Homo sapiens
Manually annotated by BRENDA team
Sheppard, D.N.; Welsh, M.J.
Structure and function of the CFTR chloride channel
Physiol. Rev.
79
S23-45
1999
Homo sapiens, Mus musculus, shark, Xenopus sp.
Manually annotated by BRENDA team
Schwiebert, E.M.; Benos, D.J.; Egan, M.E.; Stutts, M.J.; Guggino, W.B.
CFTR is a conductance regulator as well as a chloride channel
Physiol. Rev.
79
S145-166
1999
Homo sapiens
Manually annotated by BRENDA team
Weinreich, F.; Riordan, J.R.; Nagel, G.
Dual effects of ADP and adenylylimidodiphosphate on CFTR channel kinetics show binding to two different nucleotide binding sites
J. Gen. Physiol.
114
55-70
1999
Homo sapiens
Manually annotated by BRENDA team
Illek, B.; Fischer, H.; Machen, T.E.
Genetic disorders of membrane transport. II. Regulation of CFTR by small molecules including HCO3
Am. J. Physiol.
275
G1221-1226
1998
Homo sapiens
Manually annotated by BRENDA team
Seibert, F.S.; Chang, X.B.; Aleksandrov, A.A.; Clarke, D.M.; Hanrahan, J.W.; Riordan, J.R.
Influence of phosphorylation by protein kinase A on CFTR at the cell surface and endoplasmic reticulum
Biochim. Biophys. Acta
1461
275-283
1999
Homo sapiens
Manually annotated by BRENDA team
Bear, C.E.; Li, C.; Galley, K.; Wang, Y.; Garami, E.; Ramjeesingh, M.
Coupling of ATP hydrolysis with channel gating by purified, reconstituted CFTR
J. Bioenerg. Biomembr.
29
465-473
1997
Homo sapiens
Manually annotated by BRENDA team
Naren, A.P.; Di, A.; Cormet-Boyaka, E.; Boyaka, P.N.; McGhee, J.R.; Zhou, W.; Akagawa, K.; Fujiwara, T.; Thome, U.; Engelhardt, J.F.; Nelson, D.J.; Kirk, K.L.
Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl(-) currents
J. Clin. Invest.
105
377-386
2000
Homo sapiens
Manually annotated by BRENDA team
Naren, A.P.; Quick, M.W.; Collawn, J.F.; Nelson, D.J.; Kirk, K.L.
Syntaxin 1A inhibits CFTR chloride channels by means of domain-specific protein-protein interactions
Proc. Natl. Acad. Sci. USA
95
10972-10977
1998
Homo sapiens
Manually annotated by BRENDA team
Chen, M.; Zhang, J.T.
Membrane insertion, processing, and topology of cystic fibrosis transmembrane conductance regulator (CFTR) in microsomal membranes
Mol. Membr. Biol.
13
33-40
1996
Homo sapiens
Manually annotated by BRENDA team
Tusnady, G.E.; Bakos, E.; Varadi, A.; Sarkadi, B.
Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters
FEBS Lett.
402
1-3
1997
Homo sapiens
Manually annotated by BRENDA team
Price, M.P.; Ishihara, H.; Sheppard, D.N.; Welsh, M.J.
Function of Xenopus cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels and use of human-Xenopus chimeras to investigate the pore properties of CFTR
J. Biol. Chem.
271
25184-25191
1996
Homo sapiens, Xenopus sp.
Manually annotated by BRENDA team
Quinton, P.M.; Reddy, M.M.
Control of CFTR chloride conductance by ATP levels through non-hydrolytic binding
Nature
360
79-81
1992
Homo sapiens
Manually annotated by BRENDA team
Van Kuijck, M.A.; van Aubel, R.A.M.H.; Busch, A.E.; Lang, F.; Russell, F.G.M.; Bindels, R.J.M.; van Os, C.H.; Deen, P.M.T.
Molecular cloning and expression of a cyclic AMP-activated chloride conductance regulator: a novel ATP binding cassette transporter
Proc. Natl. Acad. Sci. USA
93
5401-5406
1996
Oryctolagus cuniculus, Homo sapiens
Manually annotated by BRENDA team
Kleizen, B.; Braakman, I.; de Jonge, H.R.
Regulated trafficking of the CFTR chloride channel
Eur. J. Cell Biol.
79
544-556
2000
Homo sapiens
Manually annotated by BRENDA team
Annereau, J.P.; Ko, Y.H.; Pedersen, P.L.
Cystic fibrosis transmembrane conductance regulator: the NBF1+R (nucleotide-binding fold 1 and regulatory domain) segment acting alone catalyses a Co2+/Mn2+/Mg2+-ATPase activity markedly inhibited by both Cd2+ and the transition-state analogue orthovanadate
Biochem. J.
371
451-462
2003
Homo sapiens
Manually annotated by BRENDA team
Howell, L.D.; Borchardt, R.; Kole, J.; Kaz, A.M.; Randak, C.; Cohn, J.A.
Protein kinase A regulates ATP hydrolysis and dimerization by a CFTR (cystic fibrosis transmembrane conductance regulator) domain
Biochem. J.
378
151-159
2004
Homo sapiens
Manually annotated by BRENDA team
Ramjeesingh, M.; Li, C.; Kogan, I.; Wang, Y.; Huan, L.J.; Bear, C.E.
A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator
Biochemistry
40
10700-10706
2001
Homo sapiens
Manually annotated by BRENDA team
Ketchum, C.J.; Rajendrakumar, G.V.; Maloney, P.C.
Characterization of the adenosinetriphosphatase and transport activities of purified cystic fibrosis transmembrane conductance regulator
Biochemistry
43
1045-1053
2004
Homo sapiens
Manually annotated by BRENDA team
Kogan, I.; Ramjeesingh, M.; Huan, L.J.; Wang, Y.; Bear, C.E.
Perturbation of the pore of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits its ATPase activity
J. Biol. Chem.
276
11575-11581
2001
Homo sapiens
Manually annotated by BRENDA team
Kidd Jackie, F.; Ramjeesingh, M.; Stratford, F.; Huan, L.J.; Bear Christine, E.
A heteromeric complex of the two nucleotide binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) mediates ATPase activity
J. Biol. Chem.
279
41664-41669
2004
Homo sapiens
Manually annotated by BRENDA team
Vergani, P.; Nairn, A.C.; Gadsby, D.C.
On the mechanism of MgATP-dependent gating of CFTR Cl- channels
J. Gen. Physiol.
121
17-36
2003
Homo sapiens
Manually annotated by BRENDA team
Fang, X.; Song, Y.; Hirsch, J.; Galietta, L.J.; Pedemonte, N.; Zemans, R.L.; Dolganov, G.; Verkman, A.S.; Matthay, M.A.
Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells
Am. J. Physiol. Lung Cell Mol. Physiol.
290
L242-L249
2006
Homo sapiens
Manually annotated by BRENDA team
van Barneveld, A.; Stanke, F.; Ballmann, M.; Naim, H.Y.; Tuemmler, B.
Ex vivo biochemical analysis of CFTR in human rectal biopsies
Biochim. Biophys. Acta
1762
393-397
2006
Homo sapiens
Manually annotated by BRENDA team
Fuller, M.D.; Zhang, Z.R.; Cui, G.; McCarty, N.A.
The block of CFTR by scorpion venom is state-dependent
Biophys. J.
89
3960-3975
2005
Homo sapiens
Manually annotated by BRENDA team
Galietta, L.J.; Moran, O.
Identification of CFTR activators and inhibitors: chance or design?
Curr. Opin. Pharmacol.
4
497-503
2004
Homo sapiens
Manually annotated by BRENDA team
Himmel, B.; Nagel, G.
Protein kinase-independent activation of CFTR by phosphatidylinositol phosphates
EMBO Rep.
5
85-90
2004
Homo sapiens
Manually annotated by BRENDA team
Linsdell, P.
Mechanism of chloride permeation in the cystic fibrosis transmembrane conductance regulator chloride channel
Exp. Physiol.
91
123-129
2006
Homo sapiens
Manually annotated by BRENDA team
Yan, W.; Samaha, F.F.; Ramkumar, M.; Kleyman, T.R.; Rubenstein, R.C.
Cystic fibrosis transmembrane conductance regulator differentially regulates human and mouse epithelial sodium channels in Xenopus oocytes
J. Biol. Chem.
279
23183-23192
2004
Homo sapiens
Manually annotated by BRENDA team
Rosenberg, M.F.; Kamis, A.B.; Aleksandrov, L.A.; Ford, R.C.; Riordan, J.R.
Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR)
J. Biol. Chem.
279
39051-39057
2004
Homo sapiens
Manually annotated by BRENDA team
Fischer, H.; Machen, T.E.; Widdicombe, J.H.; Carlson, T.J.; King, S.R.; Chow, J.W.; Illek, B.
A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells
J. Ethnopharmacol.
93
351-357
2004
Homo sapiens
Manually annotated by BRENDA team
Csanady, L.; Seto-Young, D.; Chan, K.W.; Cenciarelli, C.; Angel, B.B.; Qin, J.; McLachlin, D.T.; Krutchinsky, A.N.; Chait, B.T.; Nairn, A.C.; Gadsby, D.C.
Preferential phosphorylation of R-domain Serine 768 dampens activation of CFTR channels by PKA
J. Gen. Physiol.
125
171-186
2005
Homo sapiens
Manually annotated by BRENDA team
Csanady, L.; Chan, K.W.; Nairn, A.C.; Gadsby, D.C.
Functional roles of nonconserved structural segments in CFTRs NH2-terminal nucleotide binding domain
J. Gen. Physiol.
125
43-55
2005
Homo sapiens
Manually annotated by BRENDA team
Carvalho-Oliveira, I.; Efthymiadou, A.; Malho, R.; Nogueira, P.; Tzetis, M.; Kanavakis, E.; Amaral, M.D.; Penque, D.
CFTR localization in native airway cells and cell lines expressing wild-type or F508del-CFTR by a panel of different antibodies
J. Histochem. Cytochem.
52
193-203
2004
Homo sapiens
Manually annotated by BRENDA team
Stratford, F.L.; Ramjeesingh, M.; Cheung, J.C.; Huan, L.J.; Bear, C.E.
The Walker B motif of the second nucleotide-binding domain (NBD2) of CFTR plays a key role in ATPase activity by the NBD1-NBD2 heterodimer
Biochem. J.
401
581-586
2007
Homo sapiens
Manually annotated by BRENDA team
Ramjeesingh, M.; Ugwu, F.; Stratford, F.L.; Huan, L.J.; Li, C.; Bear, C.E.
The intact CFTR protein mediates ATPase rather than adenylate kinase activity
Biochem. J.
412
315-321
2008
Homo sapiens
Manually annotated by BRENDA team
Chang, Y.T.; Chang, M.C.; Su, T.C.; Liang, P.C.; Su, Y.N.; Kuo, C.H.; Wei, S.C.; Wong, J.M.
Association of cystic fibrosis transmembrane conductance regulator (CFTR) mutation/variant/haplotype and tumor necrosis factor (TNF) promoter polymorphism in hyperlipidemic pancreatitis
Clin. Chem.
54
131-138
2008
Homo sapiens
Manually annotated by BRENDA team
Mense, M.; Vergani, P.; White, D.M.; Altberg, G.; Nairn, A.C.; Gadsby, D.C.
In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer
EMBO J.
25
4728-4739
2006
Homo sapiens (P13569)
Manually annotated by BRENDA team
Beck, E.J.; Yang, Y.; Yaemsiri, S.; Raghuram, V.
Conformational changes in a pore-lining helix coupled to cystic fibrosis transmembrane conductance regulator channel gating
J. Biol. Chem.
283
4957-4966
2008
Homo sapiens
Manually annotated by BRENDA team
Bompadre, S.G.; Li, M.; Hwang, T.C.
Mechanism of G551D-CFTR (cystic fibrosis transmembrane conductance regulator) potentiation by a high affinity ATP analog
J. Biol. Chem.
283
5364-5369
2008
Homo sapiens (P13569)
Manually annotated by BRENDA team
Zhou, Z.; Wang, X.; Liu, H.Y.; Zou, X.; Li, M.; Hwang, T.C.
The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics
J. Gen. Physiol.
128
413-422
2006
Homo sapiens (P13569)
Manually annotated by BRENDA team
Ferrera, L.; Pincin, C.; Moran, O.
Characterization of a 7,8-benzoflavone double effect on CFTR Cl(-) channel activity
J. Membr. Biol.
220
1-9
2007
Homo sapiens
Manually annotated by BRENDA team
Cui, L.; Aleksandrov, L.; Hou, Y.; Gentzsch, M.; Chen, J.; Riordan, J.R.; Aleksandrov, A.A.
The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating
J. Physiol.
572
347-358
2006
Homo sapiens
Manually annotated by BRENDA team
Scott-Ward, T.S.; Cai, Z.; Dawson, E.S.; Doherty, A.; Da Paula, A.C.; Davidson, H.; Porteous, D.J.; Wainwright, B.J.; Amaral, M.D.; Sheppard, D.N.; Boyd, A.C.
Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR
Proc. Natl. Acad. Sci. USA
104
16365-16370
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Serohijos, A.W.; Hegedus, T.; Aleksandrov, A.A.; He, L.; Cui, L.; Dokholyan, N.V.; Riordan, J.R.
Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function
Proc. Natl. Acad. Sci. USA
105
3256-3261
2008
Homo sapiens
Manually annotated by BRENDA team
Bajmoczi, M.; Gadjeva, M.; Alper, S.L.; Pier, G.; Golan, D.E.
Cystic fibrosis transmembrane conductance regulator and caveolin-1 regulate epithelial cell internalization of Pseudomonas aeruginosa
Am. J. Physiol. Cell Physiol.
297
C263-C277
2009
Homo sapiens
Manually annotated by BRENDA team
Aleksandrov, L.; Aleksandrov, A.; Riordan, J.R.
Mg2+-dependent ATP occlusion at the first nucleotide-binding domain (NBD1) of CFTR does not require the second (NBD2)
Biochem. J.
416
129-136
2008
Homo sapiens
Manually annotated by BRENDA team
Shamsuddin, A.K.; Reddy, M.M.; Quinton, P.M.
Iontophoretic beta-adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo
Exp. Physiol.
93
969-981
2008
Homo sapiens
Manually annotated by BRENDA team
Sun, F.; Mi, Z.; Condliffe, S.B.; Bertrand, C.A.; Gong, X.; Lu, X.; Zhang, R.; Latoche, J.D.; Pilewski, J.M.; Robbins, P.D.; Frizzell, R.A.
Chaperone displacement from mutant cystic fibrosis transmembrane conductance regulator restores its function in human airway epithelia
FASEB J.
22
3255-3263
2008
Homo sapiens
Manually annotated by BRENDA team
Bijvelds, M.J.; Bot, A.G.; Escher, J.C.; de Jonge, H.R.
Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator
Gastroenterology
137
976-985
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
He, L.; Aleksandrov, A.A.; Serohijos, A.W.; Hegedus, T.; Aleksandrov, L.A.; Cui, L.; Dokholyan, N.V.; Riordan, J.R.
Multiple membrane-cytoplasmic domain contacts in the cystic fibrosis transmembrane conductance regulator (CFTR) mediate regulation of channel gating
J. Biol. Chem.
283
26383-26390
2008
Homo sapiens
Manually annotated by BRENDA team
Mio, K.; Ogura, T.; Mio, M.; Shimizu, H.; Hwang, T.C.; Sato, C.; Sohma, Y.
Three-dimensional reconstruction of human cystic fibrosis transmembrane conductance regulator chloride channel revealed an ellipsoidal structure with orifices beneath the putative transmembrane domain
J. Biol. Chem.
283
30300-30310
2008
Homo sapiens
Manually annotated by BRENDA team
Fatehi, M.; Linsdell, P.
State-dependent access of anions to the cystic fibrosis transmembrane conductance regulator chloride channel pore
J. Biol. Chem.
283
6102-6109
2008
Homo sapiens
Manually annotated by BRENDA team
Segal, I.; Yaakov, Y.; Adler, S.N.; Blau, H.; Broide, E.; Santo, M.; Yahav, Y.; Klar, A.; Lerner, A.; Aviram, M.; Ellis, I.; Mountford, R.; Shteyer, E.; Kerem, E.; Wilschanski, M.
Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis
J. Clin. Gastroenterol.
42
810-814
2008
Homo sapiens
Manually annotated by BRENDA team
Wang, X.; Bompadre, S.G.; Li, M.; Hwang, T.C.
Mutations at the signature sequence of CFTR create a Cd(2+)-gated chloride channel
J. Gen. Physiol.
133
69-77
2009
Homo sapiens
Manually annotated by BRENDA team
Huang, S.Y.; Bolser, D.; Liu, H.Y.; Hwang, T.C.; Zou, X.
Molecular modeling of the heterodimer of human CFTRs nucleotide-binding domains using a protein-protein docking approach
J. Mol. Graph. Model.
27
822-828
2009
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Hwang, T.C.; Sheppard, D.N.
Gating of the CFTR Cl- channel by ATP-driven nucleotide-binding domain dimerisation
J. Physiol.
587
2151-2161
2009
Homo sapiens
Manually annotated by BRENDA team
Aleksandrov, A.A.; Cui, L.; Riordan, J.R.
Relationship between nucleotide binding and ion channel gating in cystic fibrosis transmembrane conductance regulator
J. Physiol.
587
2875-2886
2009
Homo sapiens
Manually annotated by BRENDA team
Rosser, M.F.; Grove, D.E.; Chen, L.; Cyr, D.M.
Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2
Mol. Biol. Cell
19
4570-4579
2008
Homo sapiens
Manually annotated by BRENDA team
Barriere, H.; Bagdany, M.; Bossard, F.; Okiyoneda, T.; Wojewodka, G.; Gruenert, D.; Radzioch, D.; Lukacs, G.L.
Revisiting the role of CFTR and counterion permeability in the pH regulation of endocytic organelles
Mol. Biol. Cell
20
3125-3141
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Wellhauser, L.; Chiaw, P.K.; Pasyk, S.; Li, C.; Ramjeesingh, M.; Bear, C.E.
A small-molecule modulator interacts directly with DELTAPhe508-CFTR to modify its ATPase activity and conformational stability
Mol. Pharmacol.
75
1430-1438
2009
Homo sapiens
Manually annotated by BRENDA team
Muallem, D.; Vergani, P.
Review. ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator
Philos. Trans. R. Soc. Lond. B Biol. Sci.
364
247-255
2009
Homo sapiens
Manually annotated by BRENDA team
Jordan, I.K.; Kota, K.C.; Cui, G.; Thompson, C.H.; McCarty, N.A.
Evolutionary and functional divergence between the cystic fibrosis transmembrane conductance regulator and related ATP-binding cassette transporters
Proc. Natl. Acad. Sci. USA
105
18865-18870
2008
Homo sapiens
Manually annotated by BRENDA team
Midha, S.; Khajuria, R.; Shastri, S.; Kabra, M.; Garg, P.K.
Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations
Gut
59
800-807
2010
Homo sapiens
Manually annotated by BRENDA team
Lewis, H.A.; Wang, C.; Zhao, X.; Hamuro, Y.; Conners, K.; Kearins, M.C.; Lu, F.; Sauder, J.M.; Molnar, K.S.; Coales, S.J.; Maloney, P.C.; Guggino, W.B.; Wetmore, D.R.; Weber, P.C.; Hunt, J.F.
Structure and dynamics of NBD1 from CFTR characterized using crystallography and hydrogen/deuterium exchange mass spectrometry
J. Mol. Biol.
396
406-430
2010
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Kelly, M.; Trudel, S.; Brouillard, F.; Bouillaud, F.; Colas, J.; Nguyen-Khoa, T.; Ollero, M.; Edelman, A.; Fritsch, J.
Cystic fibrosis transmembrane regulator inhibitors CFTR(inh)-172 and GlyH-101 target mitochondrial functions, independently of chloride channel inhibition
J. Pharmacol. Exp. Ther.
333
60-69
2010
Homo sapiens
Manually annotated by BRENDA team
El Hiani, Y.; Linsdell, P.
Role of the juxtamembrane region of cytoplasmic loop 3 in the gating and conductance of the cystic fibrosis transmembrane conductance regulator chloride channel
Biochemistry
51
3971-3981
2012
Homo sapiens
Manually annotated by BRENDA team
Galfre, E.; Galeno, L.; Moran, O.
A potentiator induces conformational changes on the recombinant CFTR nucleotide binding domains in solution
Cell. Mol. Life Sci.
69
3701-3713
2012
Homo sapiens
Manually annotated by BRENDA team
Cho, H.J.; Gee, H.Y.; Baek, K.H.; Ko, S.K.; Park, J.M.; Lee, H.; Kim, N.D.; Lee, M.G.; Shin, I.
A small molecule that binds to an ATPase domain of Hsc70 promotes membrane trafficking of mutant cystic fibrosis transmembrane conductance regulator
J. Am. Chem. Soc.
133
20267-20276
2011
Homo sapiens
Manually annotated by BRENDA team
Tsai, M.F.; Jih, K.Y.; Shimizu, H.; Li, M.; Hwang, T.C.
Optimization of the degenerated interfacial ATP binding site improves the function of disease-related mutant cystic fibrosis transmembrane conductance regulator (CFTR) channels
J. Biol. Chem.
285
37663-37671
2010
Homo sapiens
Manually annotated by BRENDA team
Wang, W.; Linsdell, P.
Alternating access to the transmembrane domain of the ATP-binding cassette protein cystic fibrosis transmembrane conductance regulator (ABCC7)
J. Biol. Chem.
287
10156-10165
2012
Homo sapiens
Manually annotated by BRENDA team
Bai, Y.; Li, M.; Hwang, T.C.
Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7)
J. Gen. Physiol.
138
495-507
2011
Homo sapiens
Manually annotated by BRENDA team
Shimizu, H.; Yu, Y.C.; Kono, K.; Kubota, T.; Yasui, M.; Li, M.; Hwang, T.C.; Sohma, Y.
A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR
J. Physiol. Sci.
60
353-362
2010
Homo sapiens
Manually annotated by BRENDA team
Krasilnikov, O.V.; Sabirov, R.Z.; Okada, Y.
ATP hydrolysis-dependent asymmetry of the conformation of CFTR channel pore
J. Physiol. Sci.
61
267-278
2011
Homo sapiens
Manually annotated by BRENDA team
Gout, T.
Role of ATP binding and hydrolysis in the gating of the cystic fibrosis transmembrane conductance regulator
Ann. Thorac. Med.
7
115-121
2012
Homo sapiens (P13569)
Manually annotated by BRENDA team
Wang, G.
Molecular basis for Fe(III)-independent curcumin potentiation of cystic fibrosis transmembrane conductance regulator activity
Biochemistry
54
2828-2840
2015
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Zhang, J.; Hwang, T.C.
The fifth transmembrane segment of cystic fibrosis transmembrane conductance regulator contributes to its anion permeation pathway
Biochemistry
54
3839-3850
2015
Homo sapiens (P13569)
Manually annotated by BRENDA team
Cui, G.; Freeman, C.S.; Knotts, T.; Prince, C.Z.; Kuang, C.; McCarty, N.A.
Two salt bridges differentially contribute to the maintenance of cystic fibrosis transmembrane conductance regulator (CFTR) channel function
J. Biol. Chem.
288
20758-20767
2013
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Randak, C.O.; Dong, Q.; Ver Heul, A.R.; Elcock, A.H.; Welsh, M.J.
ATP and AMP mutually influence their interaction with the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) at separate binding sites
J. Biol. Chem.
288
27692-27701
2013
Homo sapiens (P13569)
Manually annotated by BRENDA team
Wei, S.; Roessler, B.C.; Chauvet, S.; Guo, J.; Hartman, J.L.; Kirk, K.L.
Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps
J. Biol. Chem.
289
19942-19957
2014
Homo sapiens (P13569)
Manually annotated by BRENDA team
Dong, Q.; Ernst, S.E.; Ostedgaard, L.S.; Shah, V.S.; Ver Heul, A.R.; Welsh, M.J.; Randak, C.O.
Mutating the conserved Q-loop glutamine 1291 selectively disrupts adenylate kinase-dependent channel gating of the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) and reduces channel function in prima
J. Biol. Chem.
290
14140-14153
2015
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Corradi, V.; Vergani, P.; Tieleman, D.P.
Cystic fibrosis transmembrane conductance regulator (CFTR): closed and open state channel models
J. Biol. Chem.
290
22891-22906
2015
Homo sapiens (P13569)
Manually annotated by BRENDA team
Lin, W.Y.; Jih, K.Y.; Hwang, T.C.
A single amino acid substitution in CFTR converts ATP to an inhibitory ligand
J. Gen. Physiol.
144
311-320
2014
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Gao, X.; Hwang, T.C.
Localizing a gate in CFTR
Proc. Natl. Acad. Sci. USA
112
2461-2466
2015
Homo sapiens (P13569)
Manually annotated by BRENDA team
Aleksandrov, L.A.; Fay, J.F.; Riordan, J.R.
R-domain phosphorylation by protein kinase A stimulates dissociation of unhydrolyzed ATP from the first nucleotide-binding site of the cystic fibrosis transmembrane conductance regulator
Biochemistry
57
5073-5075
2018
Homo sapiens
Manually annotated by BRENDA team
Hildebrandt, E.; Khazanov, N.; Kappes, J.C.; Dai, Q.; Senderowitz, H.; Urbatsch, I.L.
Specific stabilization of CFTR by phosphatidylserine
Biochim. Biophys. Acta
1859
289-293
2017
Homo sapiens
Manually annotated by BRENDA team
Odera, M.; Furuta, T.; Sohma, Y.; Sakurai, M.
Molecular dynamics simulation study on the structural instability of the most common cystic fibrosis-associated mutant DELTAF508-CFTR
Biophys. Physicobiol.
15
33-44
2018
Homo sapiens
Manually annotated by BRENDA team
El Hiani, Y.; Negoda, A.; Linsdell, P.
Cytoplasmic pathway followed by chloride ions to enter the CFTR channel pore
Cell. Mol. Life Sci.
73
1917-1925
2016
Homo sapiens
Manually annotated by BRENDA team
Moran, O.
The gating of the CFTR channel
Cell. Mol. Life Sci.
74
85-92
2017
Homo sapiens
Manually annotated by BRENDA team
Hoffmann, B.; Elbahnsi, A.; Lehn, P.; Decout, J.L.; Pietrucci, F.; Mornon, J.P.; Callebaut, I.
Combining theoretical and experimental data to decipher CFTR 3D structures and functions
Cell. Mol. Life Sci.
75
3829-3855
2018
Homo sapiens
Manually annotated by BRENDA team
Linsdell, P.
Cystic fibrosis transmembrane conductance regulator (CFTR) Making an ion channel out of an active transporter structure
Channels
12
284-290
2018
Homo sapiens
Manually annotated by BRENDA team
Wei, S.; Roessler, B.C.; Icyuz, M.; Chauvet, S.; Tao, B.; Hartman, J.L.; Kirk, K.L.
Long-range coupling between the extracellular gates and the intracellular ATP binding domains of multidrug resistance protein pumps and cystic fibrosis transmembrane conductance regulator channels
FASEB J.
30
1247-1262
2016
Homo sapiens
Manually annotated by BRENDA team
Xie, C.; Cao, X.; Chen, X.; Wang, D.; Zhang, W.K.; Sun, Y.; Hu, W.; Zhou, Z.; Wang, Y.; Huang, P.
Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia
FASEB J.
30
1579-1589
2016
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Wang, G.; Linsley, R.; Norimatsu, Y.
External Zn2+ binding to cysteine-substituted cystic fibrosis transmembrane conductance regulator constructs regulates channel gating and curcumin potentiation
FEBS J.
283
2458-2475
2016
Homo sapiens
Manually annotated by BRENDA team
Zwick, M.; Esposito, C.; Hellstern, M.; Seelig, A.
How phosphorylation and ATPase activity regulate anion flux though the cystic fibrosis transmembrane conductance regulator (CFTR)
J. Biol. Chem.
291
14483-14498
2016
Homo sapiens
Manually annotated by BRENDA team
Ehrhardt, A.; Chung, W.J.; Pyle, L.C.; Wang, W.; Nowotarski, K.; Mulvihill, C.M.; Ramjeesingh, M.; Hong, J.; Velu, S.E.; Lewis, H.A.; Atwell, S.; Aller, S.; Bear, C.E.; Lukacs, G.L.; Kirk, K.L.; Sorscher, E.J.
Channel gating regulation by the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop
J. Biol. Chem.
291
1854-1865
2016
Homo sapiens
Manually annotated by BRENDA team
Wang, C.; Aleksandrov, A.A.; Yang, Z.; Forouhar, F.; Proctor, E.A.; Kota, P.; An, J.; Kaplan, A.; Khazanov, N.; Boel, G.; Stockwell, B.R.; Senderowitz, H.; Dokholyan, N.V.; Riordan, J.R.; Brouillette, C.G.; Hunt, J.F.
Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator
J. Biol. Chem.
293
17685-17704
2018
Homo sapiens (P13569), Homo sapiens
Manually annotated by BRENDA team
Chen, J.H.; Xu, W.; Sheppard, D.N.
Altering intracellular pH reveals the kinetic basis of intraburst gating in the CFTR Cl- channel
J. Physiol.
595
1059-1076
2017
Homo sapiens
Manually annotated by BRENDA team